Flunixin is the only NSAID approved for use in cattle in the United States and is labeled for the modulation of inflammation in endotoxemia and for the control of pyrexia associated with bovine respiratory tract disease and acute bovine mastitis.1 Although flunixin is approved for use in adult cattle, there is not a specific approval for its use in calves that are to be processed for veal. However, the drug is occasionally used in an extralabel manner as a supportive treatment for calf diarrhea or pneumonia.2–4 In the United States, drug residues in human food products derived from animals cannot persist at concentrations greater than those established as safe by regulatory agencies. The greatest concentration of a drug residue allowed in edible tissue is called the tolerance limit. The tolerance limit for flunixin in adult cattle is 0.025 μg/mL (25 ppb) for muscle and 0.125 μg/mL (125 ppb) for liver.1 Because flunixin is not specifically labeled for use in veal calves, tolerance limits (and slaughter withdrawal intervals) have not been established, and any flunixin residue detected in veal calves is considered a violation. Therefore, the unofficial tolerance limit becomes less than the lowest concentration of the drug that can be detected by the analytic method used.
Flunixin residue violations are not uncommon in veal calves. In 2010, flunixin residue violations in veal calves accounted for 60 of the 285 (21%) flunixin residue violations in cattle as reported by the USDA-FSIS.5 From 2006 through 2012, 261 violative flunixin residues were detected in bob veal (meat from calves ≤ 3 weeks old or ≤ 68 kg6), which made flunixin the third most frequently identified drug residue in that type of meat behind neomycin and sulfonamides. Nonsteroi dal anti-inflammatory drugs, particularly flunixin, are widely used in the cattle industry. In a 2007 survey2 of bovine practitioners, 86% of the cattle treated with NSAIDS were dairy cattle. Similarly, results of an earlier survey3 of dairy veterinarians indicate that NSAIDs were the second most prescribed drug in dairy cattle behind antimicrobials. Because of the high incidence of violative flunixin residues in cattle, it is regularly included on the FSIS repeat violator list.7 In adult cattle, the majority of violative flunixin residues have been attributed to noncompliant drug use8,9 and impaired tissue elimination subsequent to disease processes.10 Data to predict appropriate slaughter withdrawal intervals for flunixin following administration to veal calves are limited. Furthermore, marked differences in drug pharmacokinetics have been observed between young and adult animals.11 Differences in drug distribution and elimination in young food-producing animals are of particular concern because they may increase the likelihood of violative drug residues. The primary objective of the study reported here was to examine the pharmacokinetics and tissue elimination of flunixin in veal calves following multiple IV injections of the drug so that a suggested withdrawal interval for flunixin in veal calves could be determined.
Supported by the Food Animal Residue Avoidance and Depletion Program. Patrick Brinson was supported by the Merial Veterinary Scholars Program Summer Research Internship at the College of Veterinary Medicine, North Carolina State University.
Maximal concentration of a drug
Food Safety and Inspection Service
Limit of detection
Limit of quantification
Mean residence time
Ultraperformance liquid chromatography
Banamine, Merck Animal Health, Madison, NJ.
TurboVap LV evaporator, Zymark Corp, Hopkinton, Mass.
Acquity I class UPLC with an HSS T3 column (1.8 μm, 2.1 × 100 mm) and guard column, Waters Corp, Milford, Mass.
Xevo TQD tandem quadrupole mass spectrometer, Waters Corp, Milford, Mass.
Internal standards from Santa Cruz Biotechnology, Santa Cruz, Calif.
Bond Elut cartridge, Agilent Technologies, Lake Forest, Calif.
N-Evap, Organomation, Berlin, Mass.
Acquity UPLC-MS/MS, Waters Corp, Milford, Mass
Thermo TSQ Quantum Discovery Max tandem quadrupole mass spectrometer, Thermo Electron, West Palm Beach, Fla.
Phoenix, Pharsight Corp, St Louis, Mo.
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